My "nit-picks" are as numerically proceeds:
1) AndrAIa is the one to determine whether or not they all remain after a game is over, and I may accept this fact. However, they all ought to automatically remain wherever the game leads them for the contingency of arriving at Mainframe.
2) Enzo Matrix's yo-yo is missing after he obliterates the preying mantis virus, let alone both yo-yo's Enzo Matrix once carried on either side of his waist are entirely missing from the commencement of this episode to its conclusion.
3) Why are there A and I initials on the game Sprite icons?
4) Since when did AndrAIa decide to don jewelry? Perhaps around the same time Enzo Matrix decided to place an earring into his right ear. Speaking of which, when and why did he perform this action?
5) Of all places to have the icon it appears on the end of Enzo Matrix's sword's handle. Furthermore, the icon later appears on Enzo Matrix's kilt at the very conclusion. Make up your mind, Icon!
6) How is it Back-up consecutively appears in a prison after he had been previously abducted by an oversized bird?
7) AndrAIa notifies the concomitant Binomes that she and Enzo Matrix are leaving with the game. What of Frisket? Forgot to mention him?
8) The user is encompassed with skulls despite the fact that less than a dozen skulls were tossed at the user. Not only that, but Back-up indicates the user recovering with the sequential scene of the user just emerging from beneath the skulls. Back-up must be a psychic.
9) Enzo Matrix's yo-yo is not altered from rebooting, but everything else alters from rebooting. Does this make sense?

3) AI stands for Artificial Intelligence

4) AndrAIa has always worn jewelry. She has hair things, a necklace, and earrings when we meet her in "AndrAIa".

From "Mend & Defend" to "Game Over" Enzo Matrix could not allegedly disobey the Guardian protocol, and he simply had to enter and win all games. I refer to such comments as "he can't help it; the game has triggered his Guardian protocol," which was indicated by Mouse in "Mend & Defend." However, from "Icons" to "Number 7," as well as the commencement of "The Episode with No Name" (i.e., the trio's arrival from a game), Enzo Matrix makes it clear that he needs not enter games. In fact, he identifies himself as a renegade rather than as a Guardian. Much later on during the pre-conclusion to "End Prog" Enzo Matrix was restrained from entering an incoming game, as was Bob, except Bob willingly refused to enter the game. Is the Guardian protocol not an automatic impulse? It sounds to me as if this Guardian protocol involves individual willingness. To put it another way, a Guardian freely decides whether or not he/she is to enter and win an incoming game.

Remember that in "Game Over", Enzo changes his icon to that of a game sprite. I think you can assume that this would alter his programming, making it possible for him to decide whether or not he wants to enter a game.

The Martian characters in the beginning are obvious homages to "Mars Attacks." And Enzo after he reboots is a homage to Braveheart.

"You can't handle the tooth!" Always puts me on the floor.

The poor user! His adventuring party is just him, while the heroes get to have a whole group! At least in "Wizards, Warriors, and a Word From Our Sponsor" the sides were even.

Comment, not nit: over the course of the Episdoes, AndrAIa has lost her hearing abilities. At least, it never comes up again, after "Nullzilla" (she could hear the sound(s) the nulls were reacting too).

AndrAIa after she reboots is a homage to Xena.
As is Gabrielle type sprite.

The opening game was also a homage to "The Empire Strikes Back" (the Millenium Falcon being chased through the asteroid belt) and ST:TNG (the opening shot was of a ringed planet, just like the opening credits of TNG).

The virus reminded me of Zorak from "Space Ghost."

The old Command.Com reminded me of Mel Brooks' "2000 Year Old Man" skits.

Matrix's character was also a reference to the works of Robert E. Howard, creator of Conan the Barbarian (whose favorite saying was "Crom!").

Forgot one--Matrix's gun retracts to his leg just like Robocop.

Matrix says he'll see what repairs he can make to the system. Glitch scans for and detects multiple tears in addition to the virus that Matrix promptly deletes, thanks to Gun. Later Matrix says he patched things up as best as he could. How? Glitch is broken. Active functions like "Mend" are inoperative, and I doubt Matrix could repair much alone, with Gun or his bare hands.

The binomes of this system wear standard personal icons except Backup, whose icon is unique.

The grown AndrAIA sports a pierced "outie" navel. A navel? I guess she looked incomplete without one.

It would be very interesting to find out how Matrix acquired Eye and Gun (Gun seems to be dependent on Eye in order to work properly). Gun functions very much like a key tool, responding to verbal commands and bonding itself to Matrix's hip. It would also be interesting to find out what made Matrix stop following the Guardian protocol and become a renegade.